The Retro Synthetic Approach

In fact, the overall perspective and conception of a synthesis commences with a careful logical dissection of the target-drug-molecular skeleton into synthons. However, the disconnection of a bond within a monocyclic system shall be a retro-synthetic ring-opening phenomenon, otherwise termed as the retro-synthetic approach. Likewise, the disconnection of a bond caused in a bridged-structure would ultimately produce either a mono- or a di- substituted monocyclic structure. Sometimes, it may also be possible to accomplish two-bond disconnections taking place almost simultaneously.

A double-line arrow is invariably used to indicate a reaction written backwards—the actual reaction in reverse. The retro-synthetic approach may be expaliated with the help of the following classical example of vitamin A :

Invariably Example

Potential Synthon Skeletons

Salient Features. The various salient features of the retro-synthetic approach of vitamin A are, namely :

  • 1) Carbon-skeleton is dissected into various precursor components,
  • 2) Associated synthons are derived, and
  • 3) Dark bond-lines represent the probable location of the construction reactions. 2.2.4 Materials Required

A good, knowledgeable and academically competent research chemist is fully aware of the host of organic chemical reactions that are implied either directly or indirectly in designing synthesis. It is fairly understood and appreciated that common organic compound(s) and reagent(s) must be sourced through genuine and well-reputed manufactures round the world whose products are not only authentic but also cent-per-cent reliable and trustworthy, namely : Aldrich, Sigma, Fluka, BDH, Merck, Qualigens, Loba, and the like. Paradoxically, one may expect a, pure and reasonably good desired 'target-drug-molecule' if and only when one makes use of pure starting materials ; of course, under rigid experimental conditions.

Salient Features of Materials. Following are some of the generalized salient features of starting materials, such as :

  • 1) Chemical compounds bearing simple-linear skeletons essentially having one to six carbon atoms and one functional moiety are available commonly. Such compounds generally give rise to certain basic organic entities, for instance : aldehydes, ketones, carboxylic acids and their derivatives, alcohols, and organohalogens.
  • 2) Cyclic compounds are available rather rarely and scarcely. However, compounds that are either five-membered or six-membered cyclic ones having a single functional moiety are available abundantly.
  • 3) Aromatic compounds that are available readily include : most of the benzene structural analogues having essentially either one or two functional groups attached ; besides, having side-chains consisting of upto 4 C-atoms with one functional moiety.
  • 4) Optically active chiral molecules that are available mostly belong to natural sources, namely : simple sugars, terpenes, and amino acids.

Broadly speaking, a research chemist profusely utilizes his wisdom and skill in designing the synthesis of rather complex natural products by employing relatively small synthons comprising of 1 to 5 C-atoms. In the event, when the target-drug-molecule contains a benzene ring, the selection of an aromatic starting material is invariably the best choice. In fact, the genuine demand of a chemist to have a relatively large starting-material molecule is fairly justified so as to minimise and cut-short the number of essential construction-reactions ; but unfortunately the quantum of such molecules are absolutely rare and scarce. It has also been a regular practice in designing a synthesis to make use of either naturally occurring starting material or an already synthesized chemical entity.

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